The long-term objective of this proposal is to study the biochemical and biological properties of defective human Cytomegalovirus. Studies on the mechanism of defective virus and its DNA can provide valuable information about CMV replication, latency, and oncogenicity, the approach we have chosen to pursue is to produce is to produce defective CMV particles following serial high multiplicity of infection passages. Characterization of defective and standard CMV will be performed and analysis of their DNAs with respect to size and genetic complexity determined. In preliminary experiments we have generated CMV particles which have a buoyant density of 1.22 g/cc in CsC1 as compared to standard CMV with a buoyant density of 1.28 g/cc. Length measurements of DNA molecules from standard virus recently carried out by us as well as others indicate the molecular weight to be approximately 150 x 10 to the 6th power daltons. Characterization of defective DNA currently in progress indicates a higher buoyant density. Restriction enzyme cleavage of defective and standard CMV DNA as well as heteroduplex mapping will be used to study the nature of the defect. Since the roles of defective CMV in the maintenance of persistent infections as well as in transformation are unclear, a comparison of the transcriptional properties before viral DNA replication between defective and standard CMV will be carried out. Along these lines, the biological properties of defective CMV to transform tissue cultures cells will be tested. It is anticipated that elucidation of the synthesis and properties of defective CMV will lead to a greater understanding of the various virus-cell interactions characteristic for CMV.